Michael D. Gershon, M.D.

Professor and Chairman

Organization and development of the enteric nervous system

Our research is focused on the enteric nervous system (ENS), the intrinsic
innervation of the bowel. This is the only part of the peripheral nervous
system that is capable of mediating reflex behavior in the absence of input
from the brain or spinal cord. Our goals are to understand the organization
of the two neural plexuses that comprise the ENS, and to determine how enteric
microcircuits and the activity of individual neurons within these circuits
control the primitive motile, secretory, and absorptive behaviors of the gut.
We have devised novel techniques to study enteric microcircuits. In addition
to electrophysiology, these include optical imaging techniques with probes
that permit neuronal activity to be assessed and neuronal connections to be
identified. We also study the cellular biology and function of serotonin in
initiating enteric reflexes and signaling to the brain. These studies include
the analysis of the behavior of the gut in transgenic mice that lack individual
subtypes of serotonin receptor and/or the transporter molecule that is primarily
responsible for the inactivation of serotonin within the bowel.

In additon to studies of the adult ENS, we are investigating its development.
The ENS is known to be derived from precursors that migrate to the gut from
the neural crest. We are currently identifying the molecular signals
(guidance molecules and growth factors) utilized by to migrate correctly from
their neural crest origin to their final destinations in the bowel, to stop
migrating when they reach these destinations, and what microenvironmental cues
help to influence the phenotypic expression of neural and glial precursors within
the ENS. This work involves tissue and organ culture, the construction of
chick-quail interspecies chimeras, and work on the molecular basis of a defect
in a mutant strain of mouse that causes a segment of bowel not to be
colonized by crest-derived precursors.